Adhering to the original philosophy that has guided the Alcohol Research Center from its inception, we bring together researchers with backgrounds in biophysics, biochemistry, cell biology, molecular biology, pharmacology and pathology around the central theme of "Alcohol and the Cell". The common focus of the different research components remains the elucidation of (1) the relationship between the structural and functional effects of ethanol on cells and subcellular structures, (2) the adaptations occurring during long-term exposure of the organism to ethanol, and (3) the molecular basis for irreversible cell injury associated with long-term ethanol intake. Studies focus on a variety of different tissues, including liver, heart, brain, cell lines of different origins and model membrane systems. Techniques to be used include electron paramagnetic resonance, nuclear magnetic resonance, fluorescence lifetime and energy transfer measurements, real-time fluorescence microscopic imaging of single cells, laser confocal microscopy of signal cells and perfused organs, electron microscopy, HPLC separation of lipids (both on an analytical and preparative scale), capillary gas chromatography, single cell electrophysiological measurements (voltage clamp and patch clamp) and molecular biological techniques. Individual projects focus on the effects of ethanol on the following parameters: (1) Cell Membrane Constituents, including (a) membrane lipids, (b)protein kinase C, and (c) phospholipid pools; (2) Cellular Function, including (a) Ca2+-dependent signal transduction, (b)E-C coupling in cardiac myocytes, and (c) cardiac Ca2+ channels; (3) Cell and Tissue Injury, including (a) apoptosis, and (b) aldehyde dehydrogenase gene expression. Pilot projects for the first two years focus on (1) ethanol effects on neuronal survival and (2) ethanol effects on connexin-43 expression. We expect that these studies will contribute to elucidating the relationship between ethanol-induced alterations at the molecular and cellular levels and the development of alcohol-related diseases.